Facile Removal of Homogeneous SABRE Catalysts for Purifying Hyperpolarized Metronidazole, a Potential Hypoxia Sensor

Abstract

We report a simple and effective method to remove IrIMes homogeneous polarization transfer catalysts from solutions where NMR Signal Amplification By Reversible Exchange (SABRE) has been performed, while leaving intact the substrate's hyperpolarized state. Following microTesla SABRE hyperpolarization of ¹⁵N spins in metronidazole, addition of SiO₂ microparticles functionalized with 3-mercaptopropyl or 2-mercaptoethyl ethyl sulfide moieties provides removal of the catalyst from solution well within the hyperpolarization decay time at 0.3 T (<i>T</i> ₁>3 mins)-and enabling transfer to 9.4 T for detection of enhanced ¹⁵N signals in the absence of catalyst within the NMR-detection region. Successful catalyst removal from solution is supported by the inability to "re-hyperpolarize" ¹⁵N spins in subsequent attempts, as well as by ¹H NMR and ICP-MS. Record-high ¹⁵N nuclear polarization of up to ~34% was achieved, corresponding to >100,000-fold enhancement at 9.4 T, and approximately 5/6^th of the ¹⁵N hyperpolarization is retained after ~20-second-long purification procedure. Taken together, these results help pave the way for future studies involving <i>in vivo</i> molecular imaging using agents hyperpolarized via rapid and inexpensive parahydrogen-based methods.